University of Adelaide Library

Adelaide Research and Scholarship : Schools and Disciplines : School of Medical Sciences : Pharmacology : Pharmacology publications

Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/74168

Type: Journal article
Title: ABCB1 haplotype and OPRM1 118A > G genotype interaction in methadone maintenance treatment pharmacogenetics
Author: Barratt, Daniel Thomas
Coller, Janet Kristie
Hallinan, Richard
Byrne, Andrew
White, Jason Mark
Foster, David John Richard
Somogyi, Andrew Alexander
Citation: Pharmacogenomics and Personalized Medicine, 2012; 5(1):53-62
Publisher: Dove Medical Press
Issue Date: 2012
ISSN: 1178-7066
School/Discipline: Clinical and Experimental Pharmacology
Statement of
Responsibility: 
Daniel T. Barratt, Janet K, Coller, Richard Hallinan, Andrew Byrne, Jason M. White, David J.R. Foster and Andrew A. Somogyi
Abstract: BACKGROUND: Genetic variability in ABCB1, encoding the P-glycoprotein efflux transporter, has been linked to altered methadone maintenance treatment dose requirements. However, subsequent studies have indicated that additional environmental or genetic factors may confound ABCB1 pharmacogenetics in different methadone maintenance treatment settings. There is evidence that genetic variability in OPRM1, encoding the mu opioid receptor, and ABCB1 may interact to affect morphine response in opposite ways. This study aimed to examine whether a similar gene-gene interaction occurs for methadone in methadone maintenance treatment. METHODS: Opioid-dependent subjects (n = 119) maintained on methadone (15–300 mg/day) were genotyped for five single nucleotide polymorphisms of ABCB1 (61A > G; 1199G > A; 1236C > T; 2677G > T; 3435C > T), as well as for the OPRM1 18A > G single nucleotide polymorphism. Subjects’ methadone doses and trough plasma (R)-methadone concentrations (Ctrough) were compared between ABCB1 haplotypes (with and without controlling for OPRM1 genotype), and between OPRM1 genotypes (with and without controlling for ABCB1 haplotype). RESULTS: Among wild-type OPRM1 subjects, an ABCB1 variant haplotype group (subjects with a wild-type and 61A:1199G:1236C:2677T:3435T haplotype combination, or homozygous for the 61A:1199G:1236C:2677T:3435T haplotype) had significantly lower doses (median ± standard deviation 35 ± 5 versus 180 ± 65 mg/day, P < 0.01) and Ctrough (78 ± 22 versus 177 ± 97 ng/mL, P < 0.05) than ABCB1 wild-type subjects. Among subjects with the most common ABCB1 haplotype combination (wild-type with 61A:1199G:1236T:2677T:3435T), the OPRM1 118 A/G genotype was associated with a significantly higher Ctrough than 118 A/A (250 ± 126 versus 108 ± 36 ng/mL, P = 0.016). No ABCB1 haplotype group or OPRM1 genotype was associated with dose or Ctrough without taking into account confounding genetic variability at the other locus. Therefore, two interacting pharmacogenetic determinants of methadone maintenance treatment response were identified, ie, ABCB1, where variants are associated with lower methadone requirements, and OPRM1, where the variant is associated with higher methadone requirements. CONCLUSION: These opposing pharmacogenetic effects therefore need to be considered in combination when assessing methadone maintenance treatment pharmacogenetics.
Rights: Copyright © 2012 Dove Medical Press Ltd, All Rights Reserved.
RMID: 0020119483
DOI: 10.2147/PGPM.S29272
Appears in Collections:Pharmacology publications
View citing articles in: Google Scholar
Scopus

There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

© 2008 The University of Adelaide
library@adelaide.edu.au
CRICOS Provider Number 00123M
Service Charter | Copyright | Privacy | Disclaimer